The systemic acid-base disturbances, respiratory acidosis, metabolic alkalosis, and metabolic acidosis, are commonly observed situations in clinical medicine. An important feature of each of the above conditions is the associated renal response. In general, the 'total' kidney responses have been well described. However, there is little direct information as to many of the specific alterations in nephron function which are unique to each of the above disorders. The proposed research is intended to directly characterize certain important features of the renal response in these three situations utilizing micropuncture techniques. Specifically, we will attempt: 1) to determine the characteristics of hydrogen ion secretion in the proximal and distal convoluted tubules and to evaluate the alterations of the nephron handling of bicarbonate, chloride, potassium, and ammonia at various time intervals following the induction of respiration acidosis; 2) to determine the influence of three factors, extracellular fluid volume, potassium deficiency, and mineralocorticoids, important in the maintenance of stable metabolic alkalosis, on the characteristics of hydrogen ion secretion in the proximal and distal convoluted tubule, and to define the characteristics of the nephron response during the correction of "sodium chloride sensitive" metabolic alkalosis; and 3) to define the characteristics of hydrogen ion secretion in the proximal and distal convoluted tubule in acute and chronic metabolic acidosis, to define the segmental nephron contribution to titratable acidity and ammonia formation and bicarbonate reabsorption during these two conditions, and to examine the relationship between extracellular fluid volume expansion and the correction of chronic metabolic acidosis. In regard to the latter, we wish to examine the relationship of distal tubular sodium reabsorption and distal tubular fluid flow rate to distal tubular acid excretion.